Knef appeared in The Snows of Kilimanjaro
She had been admitted to the hospital with a lung infection, hospital officials said.
Knef's health had declined after emergency surgery last year.
"She was the voice of Berlin and one of Germany's greatest international stars," said Dieter Kosslick, the director of the Berlin film festival.
He said the festival, which opens next week, would adjust its programme to honour her.
Returning home
Knef, born in the town of Ulm, studied at the Babelsberg Film Institute and acted on stage in war-shattered Berlin immediately after the end of World War II.
She became a star for her role as a former concentration camp inmate returning home in Wolfgang Staudte's 1946 Murderers Are Among Us.
Knef, who sometimes appeared as Hildegard Neff in the United States, appeared in more than 50 films, most of them made in Europe.
She reportedly turned down a Hollywood studio contract after being told she would have to change her name and say she was Austrian, not German.
She scandalised Roman Catholic authorities with a brief nude scene in the 1951 German film The Story of a Sinner, in which she played a prostitute.
Supporting role
Among her other film credits was as Pirate Jenny in a 1962 version of The Threepenny Opera and as Catherine the Great in Catherine of Russia.
Her work in the US included the role of Ninotchka in Cole Porter's Broadway musical Silk Stockings in the 1950s, and a supporting role in The Snows of Kilimanjaro, an adaptation of the Ernest Hemingway story that starred Gregory Peck and Ava Gardner.
Knef launched a career as a singer in the 1960s and wrote a best-selling 1970 autobiography.
She continued to act and sing almost until the end of her life, appearing as herself in the 2000 documentary Marlene Dietrich: Her Own Song, and in the 1999 German comedy An Almost Perfect Wedding.
Marriages to the American Kurt Hirsch and British actor David Cameron ended in divorce.
She is survived by her husband, Paul von Schell, and a daughter, Christina Antonia.